A multi-institutional study of extracorporeal photophoresis (ECP) with Uvadex® for the prevention of acute graft vs. host disease (aGvHD) in patients (pts) undergoing allogeneic hematopoietic progenitor cell transplants (allo-HPCT) with myeloablative conditioning

GvHD remains a major cause of morbidity and mortality after an allo-HPCT, and ECP has been shown in numerous studies to be effective in its treatment. ECP has also been used in the prevention of GvHD in a novel non-myeloablative preparative regimen for allo-HPCT (Foss, BBMT 9:96, 2003). The incidence of aGvHD was substantially reduced in this study, possibly due to the effect of ECP on host dendritic cells, causing alteration in allo-antigen presentation and reduced donor T-cell activation. We report here the preliminary results of a multi-institutional phase II study utilizing ECP with Uvadex® in a myeloablative regimen of allo-HPCT. Treatment with ECP was given on any two days from Day -10 to -6, followed by cyclophosphamide 60mg/kg for 2 days and TBI 1200 cGy over three days. Pts. received cyclosporine (CSA) 3–5mg/kg iv from Day -1 (and switched later to PO), to keep levels between 200–600 ng/ml, and methotrexate 10mg/m2 on Days 1,3,6 and 11 for matched unrelated donors (MUD) and one antigen mismatched related donors, and 10mg/m2 on Day 1 and 5mg/m2 on Days 3,6 and 11 in matched related donors (MRD), as GvHD prophylaxis. CSA was continued until Day 100 and then tapered. Data is available on 34 of 50 enrolled pts. Nineteen pts. are male and the median age is 37 (range 20 –58). Diagnosis leading to HPCT includes acute leukemia and myelodysplasia (n = 21), chronic leukemia (n = 9), lymphoma (n = 3) and other (n = 1). Eighteen pts. received bone marrow (BM) and 16 peripheral blood (PB) HSCT. Nineteen pts. received matched unrelated or mismatched related grafts and 15 matched related. Median time to engraftment was 20 days for BM and 15 days for PB. ECP was well tolerated in 33 pts. with one pt. having mild reversible hypotension. ECP was not discontinued on any pt. At a median follow up of 85 days (range 5 to 295), acute GvHD Grade II-IV developed in 11 (35.5%) pts. (6 with BM and 5 with PB; 4 with MRD HPCT and 7 with MUD HPCT). Three pts.died (all MUD HPCT) at a median of 47 days from HPCT, two from aGvHD (Grades III and IV), and one from multi-organ failure. 31 pts. are alive while 3 have relapsed (2 with ALL and 1 NHL). This preliminary analysis shows that ECP can safely be administered to pts. undergoing myeloablative allo-HPCT. Further follow up is ongoing to assess acute and chronic GvHD rates, relapse and transplant related mortality. Pre and post-ECP lab data on T cell subsets, dendritic cells and NK cells will also be evaluated.